The objectives of this research program are to continue our studies of the control aspects of purine metabolism in whole animals, in cultured hepatocytes and in cultured human fibroblasts, to elucidate the regulation of these processes particularly as they apply to those situations where the control of purine metabolism appears defective, i.e. excess synthesis in gout, and reduced degradation of adenosine in immune deficiency. These objectives are necessary for an understanding of the way the mammal regulates the synthesis, reutilization and degradation of purines. This will be approached by studying individual components of the purine metabolizing machinery in a variety of tissues under dietary conditions known to have markedly different rates of purine biosynthesis, reutilization and degradation. These investigations will also be supplemented by studies on cultured fibroblasts from normal as well as patients with clinical gout and on lymphocytes from malnourished animals.